The spectrum of cardiac abnormalities in patients with acromegaly: results from a case-control cardiac magnetic resonance study.

PURPOSE: Cardiac abnormalities are common in patients with acromegaly, contributing to the increased morbidity and mortality. Cardiac magnetic resonance (CMR) is the gold standard for measuring cardiac morpho-functional changes. This study aims to detect cardiac alterations in acromegaly through CMR, even when the disease is adequately controlled. METHODS: In this, multicentre, case-control study, we compared consecutive patients with acromegaly, cured after surgery or requiring medical treatment, with matched controls recruited among patients harbouring non-functioning adrenal incidentalomas. RESULTS: We included 20 patients with acromegaly (7 females, mean age 50 years) and 17 controls. Indexed left ventricular-end-diastolic volume (LV-EDVi) and LV-end-systolic volume (LV-ESVi) were higher in patients than in controls (p < 0.001), as were left ventricular mass (LVMi) (p = 0.001) and LV-stroke volume (LV-SVi) (p = 0.028). Right ventricle (RV) EDVi and ESVi were higher, whereas RV-ejection fraction (RV-EF) was lower (p = 0.002) in patients than in controls (p < 0.001). No significant differences were observed in the prevalence of cardiometabolic comorbidities, including hypertension, glucose and lipid metabolism impairment, obstructive sleep apnoea syndrome, and obesity. IGF1 x upper limit of normal significantly predicted LVMi (b = 0.575; p = 0.008). Subgroup analysis showed higher LVMi (p = 0.025) and interventricular septum thickness (p = 0.003) in male than female patients, even after adjusting cardiac parameters for confounding factors. CONCLUSIONS: The CMR analysis reveals a cluster of biventricular structural and functional impairment in acromegaly, even when the biochemical control if achieved. These findings appear specifically triggered by the exposure to GH-IGF1 excess and show sex-related differences advocating a possible interaction with sex hormones in cardiac disease progression.

Cardiac magnetic resonance reveals biventricular impairment in Cushing's syndrome: a multicentre case-control study.

PURPOSE: Cushing's syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. METHODS: This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. RESULTS: Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. CONCLUSION: CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

BACKGROUND: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. METHODS AND RESULTS: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and ß-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with ß-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. CONCLUSIONS: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Myocardial extracellular volume quantification with computed tomography-current status and future outlook.

Non-invasive quantification of the extracellular volume (ECV) is a method for the evaluation of focal and diffuse myocardial fibrosis, potentially obviating the need for invasive endomyocardial biopsy. While ECV quantification with cardiac magnetic resonance imaging (ECVMRI) is already an established method, ECV quantification with CT (ECVCT) is an attractive alternative to ECVMRI, similarly using the properties of extracellular contrast media for ECV calculation. In contrast to ECVMRI, ECVCT provides a more widely available, cheaper and faster tool for ECV quantification and allows for ECV calculation also in patients with contraindications for MRI. Many studies have already shown a high correlation between ECVCT and ECVMRI and accumulating evidence suggests a prognostic value of ECVCT quantification in various cardiovascular diseases. Adding a late enhancement scan (for dual energy acquisitions) or a non-enhanced and late enhancement scan (for single-energy acquisitions) to a conventional coronary CT angiography scan improves risk stratification, requiring only minor adaptations of the contrast media and data acquisition protocols and adding only little radiation dose to the entire scan.Critical relevance statementThis article summarizes the technical principles of myocardial extracellular volume (ECV) quantification with CT, reviews the literature comparing ECVCT with ECVMRI and histopathology, and reviews the prognostic value of myocardial ECV quantification for various cardiovascular disease.Key points• Non-invasive quantification of myocardial fibrosis can be performed with CT.• Myocardial ECV quantification with CT is an alternative in patients non-eligible for MRI.• Myocardial ECV quantification with CT strongly correlates with ECV quantification using MRI.• Myocardial ECV quantification provides incremental prognostic information for various pathologies affecting the heart (e.g., cardiac amyloidosis).

Interleukin-17A-Correlated Myocarditis in Patients with Psoriasis: Cardiac Recovery following Secukinumab Administration.

(1) Background: Psoriasis (PS) is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has rarely been suggested. (2) Aims: Report of PS-related myocarditis. (3) Methods and Results: One hundred consecutive patients with PS were screened for cardiac involvement. Among them, five male patients (aged 56 ± 9.5 years) with a moderate-severe form of PS showed dilated cardiomyopathy (LVEF < 35%) with normal coronary arteries and valves. They underwent a left-ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which play a major role in PS pathogenesis. Real-time PCRs were carried out for cardiotropic viruses, and Western blot analysis was conducted for myocardial expression of IL-17A. Patients' sera were tested for anti-heart autoantibodies. Active lymphocytic myocarditis was revealed in all five patients, characterized by an absence of viral genomes with PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and enhancement of IL-17-A during western blot analysis, showing a 2.48-fold increase in psoriatic myocarditis compared with no psoriatic myocarditis and a six-fold increase compared to myocardial controls. Treatment included combination of prednisone (1 mg/kg daily for 4 weeks, tapered to 0.33 mg/kg) and azathioprine (2 mg/kg, daily) in 3 pts or secukinumab (SK, 150 mg/weekly for 4 weeks followed by 150 mg/monthly) in 2 pts for 6 months. LVEDD and LVEF improved in the first 3 pts (-14% and + 118%, respectively), while they completely recovered (LVEF > 50%) in the last 2 pts on SK. (4) Conclusions: IL-17A-related myocarditis can occur in up to 5% of patients with PS. It manifests as progressive dilated cardiomyopathy. It may completely recover following SK administration.

Infiltration of Conduction Tissue Is a Major Cause of Electrical Instability in Cardiac Amyloidosis.

BACKGROUND: The pathology of conduction tissue (CT) and relative arrhythmias in living subjects with cardiac amyloid have never been reported. AIMS: To report CT pathology and its arrhythmic correlations in human cardiac amyloidosis. METHODS AND RESULTS: In 17 out of 45 cardiac amyloid patients, a left ventricular endomyocardial biopsy included conduction tissue sections. It was identified by Aschoff-Monckeberg histologic criteria and positive immunostaining for HCN4. The degree of conduction tissue infiltration was defined as mild when ≤30%, moderate when 30-70% and severe when >70% cell area was replaced. Conduction tissue infiltration was correlated with ventricular arrhythmias, maximal wall thickness and type of amyloid protein. Mild involvement was observed in five cases, moderate in three and severe in nine. Involvement was associated with a parallel infiltration of conduction tissue artery. Conduction infiltration correlated with the severity of arrhythmias (Spearman rho = 0.8, p < 0.001). In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in seven patients with severe, one patient with moderate and none with mild conduction tissue infiltration. Pacemaker implantation was required in three patients, with complete conduction section replacement. No significant correlation was observed between the degree of conduction infiltration and age, cardiac wall thickness or type of amyloid protein. CONCLUSIONS: Amyloid-associated cardiac arrhythmias correlate with the extent of conduction tissue infiltration. Its involvement is independent from type and severity of amyloidosis, suggesting a variable affinity of amyloid protein to conduction tissue.

Effectiveness of clinical scores in predicting coronary artery disease in familial hypercholesterolemia: a coronary computed tomography angiography study.

PURPOSE: One of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH. MATERIAL AND METHODS: One-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA. MFHS, FHRS, SAFEHEART-RE and DLCN were assessed for each patient. Atherosclerotic burden scores at CCTA (Agatston score [AS], segment stenosis score [SSS]) and CAD-RADS score were calculated and compared to clinical indices. RESULTS: Non-obstructive CAD was found in 109 patients, while 30 patients had a CAD-RADS ≥ 3. Classifying the two groups according to AS, values varied significantly for MFHS (p < 0.001), FHRS (p < 0.001) and SAFEHEART-RE (p = 0.047), while according to SSS only MFHS and FHRS showed significant differences (p < 0.001). MFHS, FHRS and SAFEHEART-RE, but not DLCN, showed significant differences between the two CAD-RADS groups (p < .001). MFHS proved to have the best discriminatory power (AUC = 0.819; 0.703-0.937, p < 0.001) at ROC analysis, followed by FHRS (AUC = 0.795; 0.715-0.875, p < .0001) and SAFEHEART-RE (AUC = .725; .61-.843, p < .001). CONCLUSIONS: Greater values of MFHS, FHRS and SAFEHEART-RE are associated to higher risk of obstructive CAD and might help to select asymptomatic patients that should be referred to CCTA for secondary prevention.

Removal of cardiac AL amyloid with positive remodelling of cardiomyocytes and of restrictive cardiomyopathy.

Herein, we describe histological mobilization of light chain cardiac amyloid documented by sequential left ventricular endomyocardial biopsies. These findings were associated with positive remodelling of cardiomyocytes and of restrictive cardiomyopathy resulting from 14 courses of chemotherapy over 17 years of time. Histological and ultrastructural findings of light chain cardiac amyloid removal led to increase in cardiomyocyte dimension and electrocardiogram voltages, reduction of biventricular wall thickness with improvement of left ventricular diastolic function, and NYHA class shifting from III to I.

Hypersensitivity Myocarditis after COVID-19 mRNA Vaccination.

BACKGROUND: Myocarditis, even in a severe and lethal form, may occur after COVID-19 mRNA (BNT162b2) vaccination. However, its pathway, morphomolecular characterization and treatment are still unknown. METHODS: Routine hematochemical screening, ECG, Holter monitoring, 2D echocardiogram cardiac magnetic resonance (CMR) and invasive cardiac studies (cardiac catheterization, selective coronary angiography, left ventriculography and left ventricular endomyocardial biopsy) are reported from three patients (39F-pt1, 78M-pt2, 52M-pt3) with severe compromise of conduction tissue (junctional rhythm and syncope, pt1) or cardiac function compromise (LVEF ≤ 35%, pt2 and pt3) after COVID-19 mRNA (BNT162b2). RESULTS: Hematochemical data and coronary angiography were normal in the patients studied. Histology showed in all three patients extensive myocardial infiltration of degranulated eosinophils and elevation of serum cationic protein directly responsible for cardiomyocyte damage. These findings demonstrate myocarditis hypersensitivity to some component of the vaccine (spike protein?) acting as a hapten to some macromolecules of cardiomyocytes. Steroid administration (prednisone, 1 mg/kg die for 3 days, followed by 0.33 mg/kg for 4 weeks) was followed by complete recovery of cardiac contractility in pt2 and pt3. CONCLUSIONS: Eosinophilic myocarditis is a possible adverse reaction to the mRNA COVID-19 vaccine. Its pathway is mediated by release of cationic protein and responds to short courses of steroid administration.

False-positive bone scintigraphy denoting transthyretin amyloid in elderly hypertrophic cardiomyopathy.

A positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc-HPD) is believed to have high sensitivity (>99%) and specificity (91%) for the diagnosis of transthyretin amyloid cardiomyopathy. We report the case of an 85-year-old man with increased thickness of ventricular walls and a positive bone scintigraphy, who was unexpectedly found to have sarcomeric hypertrophic cardiomyopathy at left ventricular endomyocardial biopsy. Congo Red staining, immunohistochemistry, and transmission electronmicroscopy on six left ventricular samples scored negative for amyloidosis but were suggestive for sarcomeric hypertrophic cardiomyopathy. Genetic study did not show TTR and most commonly involved sarcomeric genes mutations. In hypertrophic cardiomyopathy focal cell necrosis related to demand/supply oxygen mismatch, small vessels disease or inflammation could be responsible of a false-positive bone scintigraphy signal for transthyretin amyloidosis. Because of this, especially in view of a possible specific treatment, endomyocardial biopsy is highly recommended for the correct diagnosis of cardiomyopathies with hypertrophic phenotype.

Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long-Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events.

Background Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH-causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long-term response to therapy and the risk of atherosclerosis. Methods and Results A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low-density lipoprotein-rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid-lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow-up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hundred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M-). The response to lipid-lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/M- and controls. Finally, after adjustments for confounders, we observed a 5-fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06-21.36; Padj=0.041). Conclusions Monogenic cause of FH is associated with lower response to conventional cholesterol-lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic-related events. Genetic testing for hypercholesterolemia is helpful in providing important prognostic information.

Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome.

We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37-year-old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, developed a dilated cardiomyopathy with ventricular tachyarrhythmias and recurrent syncope. At magnetic resonance cardiomyopathy was characterized by left ventricular dilatation with hypo-contractility and mitral prolapse with valve regurgitation. At left ventricular endomyocardial biopsy, it was documented cardiomyocyte disconnection because of cytoskeletal disorganization of cell-to-cell contacts, including intercalated discs, and mitochondrial damage and dysfunction with significant reduction of adenosine triphosphate production in patient cultured fibroblasts. At an extensive analysis by next-generation-sequencing of 4183 genes potentially related to the cardiomyopathy a pathogenic mutation of calreticulin was found. The cardiomyopathy appeared to be functionally and electrically stabilized by a combination therapy including carvedilol and amiodarone at a follow-up of 18 months.

Giant caseous mitral annular calcification mimicking ventricular pseudoaneurysm.

An 82-year-old woman with precordial pain at rest was admitted to the Emergency Department for possible cardiac heart disease; electrocardiogram excluded ischemia and high-sensitive troponin was normal. Echocardiogram revealed a hyperechoic mass adjacent to the mitral annulus. Electrocardiography-gated computed tomography (CT) angiography exam confirmed the presence of the mass protruding into the atrioventricular groove, adjacent to the posterior mitral. On the precontrast images the lesion was hyperdense with some scattered central calcific spots. CT findings are typical of a giant caseous calcification of the mitral annulus and excluded the diagnoses of pseudoaneurysm (it does not show any communication with the left ventricular cavity), neoplasm/abscess (complete caseous/calcified content) or infected/abscessified mitral calcification (absence of internal hypodense core). This is a benign condition that can be easily misdiagnosed as ventricular aneurysm or pseudoaneurysm on the contrast-enhanced images, when the caseous content is isodense to the iodinated blood pool.

Radiological outpatient' visits to avoid inappropriate cardiac CT examinations: an 8-year experience report.

PURPOSE: The aim of this study was to evaluate the appropriateness of the cardiac computed tomography angiography (CCTA) prescriptions according to the "2010-Appropriate-Use-Criteria-for-Cardiac-Computed-Tomography-Angiography" (AUCCTA) and "Clinical-indication-for-CCTA" (CICCTA) among different specialities (Cardiologist [CA], General Practitioner [GP], Other Specialists [OS]) and prescribers' age. MATERIALS AND METHODS: This is a single-centre, single-arm, cohort study. We prospectively enrolled 815 patients (October 2012-May 2019) who underwent a radiological outpatient visit, before CCTA examination. Prescriptions to the examination were categorized as follows: Appropriate (A), Uncertain (U) and Inappropriate (Ina), according to AUCCTA and I, II, III and Inv for CICCTA. This categorization was stratified according to CA, GP and OS and prescribers' age. CCTA was performed in patients whom indications belong to A/U categories. RESULTS: Eight hundred and fifteen CCTA prescriptions were analysed. An yearly increase in prescriptions was found in the eight-year observational period (2012/2019 projection: 72 vs 223). Considering AUCCTA, indication A was 540/815 (66.3%), indication U was 113/815 (13.9%) and Ina accounted for 162/815 (19.9%; 128/162 [79.0%] indications with stress test listed as criterium of inappropriateness). Only U indications decreased over years (p = 0.003). Regarding CICCTA, 501/815 (61.5%) patients were categorized as I, 144/815 (17.7%) as II, 102/815 (12.5%) as III, 67/815 (8.2%) were INV and 1/815 (0.1%) were non-classified. Clinical referrals were CA in 495/786 (63.0%), GPs in 57/786 (7.3%) GP and OS in 234/786 (29.8%) [p < 0.01]. No statistically significant differences were observed in the appropriateness among different specialty physicians. Younger doctors have a lower chance to not meet A indication (OR 0.98 [CI 95% 0.96-0.99]; p = 0.003). CONCLUSION: Our study highlights the importance of a pre-radiological visit prior to CCTA, which prevented execution of 19.9% of inappropriate examinations. Age of prescribers had an impact on appropriateness, with younger doctors having a lower chance to not meet A indication.

Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome.

AIMS: Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported. METHODS AND RESULTS: Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1ß, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1ß was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients. CONCLUSION: Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.

Use of the new Lake Louise Criteria improves CMR detection of atypical forms of acute myocarditis.

The purpose of our study was to compare diagnostic performance of old and new Lake Louise Criteria (oLLC and nLLC) among different clinical presentations: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR). 102 patients with clinical suspicion of acute myocarditis underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. Protocol included cine-SSFP, T2-weighted STIR, T2 mapping, early and late gadolinium enhancement and T1 mapping acquired before and after gadolinium administration. The degree of agreement has been calculated with Cohen's K test. 42 patients also underwent endomyocardial biopsy (EMB). IL onset was present in 54/102 patients, CM in 28/102 and AR in 20/102. nLLC were positive in 58.3% of the patients, while oLLC in 37.9%, k = 0.57 (IC: 0.428-0.713). The degree of agreement between nLLC and oLLC was 0.49 (IC: 0.111-0.876) for AR onset (nLLC positive in 35% vs oLLC in 15%), 0.25 (IC: 0.035-0.459) for CM pattern (nLLC positive in 60.7% vs oLLC 17.9%) and 0.73 (IC: 0.543-0.912) for IL presentation (nLLC positive in 66.7% vs oLLC in 57.4%). Diagnostic accuracy was 75% for both nLLC and oLLC among IL onset, and 41.6% for oLLC vs 66.7% for nLLC, as regards CM clinical presentation. nLLC have improved diagnostic performance of CMR for the diagnosis of acute myocarditis, in particular for atypical clinical presentation.

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study.

OBJECTIVES: The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis. BACKGROUND: The evolution of diabetic cardiomyopathy to heart failure affects patients'morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression. METHODS: Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up. RESULTS: A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = -35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = -20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation. CONCLUSIONS: Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237).

Myocarditis and intramural coronary vasculitis in polyarteritis nodosa: an unusual treatable form of heart failure.

We describe an uncommon cardiac presentation of polyarteritis nodosa. A 68-year-old woman, with a history of fatigue, weight loss, and myalgia of the lower extremities, was admitted for congestive heart failure. Coronary arteries were normal. Endomyocardial biopsy showed active lymphocytic myocarditis with associated intramural small vessels necrotizing vasculitis. The overexpression of TLR-4 and the negativity for myocardial viruses suggested an immune mediated mechanism of cardiac damage. These histologic findings associated to weight loss >4 kg not due to dieting or other factors, myalgias, and polyneuropathy, were consistent with the diagnosis of polyarteritis nodosa. Immunosuppressive treatment, consisting of cyclophosphamide and prednisolone, led to a significant improvement of cardiac function. Polyarteritis nodosa can be the cause of unexplained heart failure due to myocarditis and intramural vessels vasculitis. Its recognition is crucial to obtain a cardiac recovery with a tailored immunosuppressive treatment.